In the short run, eating is controlled by a number of mechanisms. First, the stomach wall has stretch receptors that signal distention as food fills the stomach. These signals are conveyed by the afferents of the vagus nerve to the solitary nucleus in the medulla. From there the information is relayed to several brain areas, including the hypothalamus, either directly or via a relay in the parabrachial nucleus, to organize autonomic responses to the ingested material, and the thalamus and cortex, for conscious awareness of the fullness of the stomach. In the hypothalamus, the paraventricular, dorsomedial, and arcuate nuclei and the lateral hypothalamus are the major targets of these signals.
Sensory afferents also sense the concentrations of glucose and lipids in the intestines and the hepatic portal circulation and send this information to the solitary nucleus and, from there, to the hypothalamus, in a manner similar to that described for the stretch receptors. In addition, the stomach and gut release a number of hormones in response to feeding, including cholecystokinin, peptide YY, glucagonlike peptide-1 (GLP-1), and ghrelin. Hypothalamic cells have receptors for many of these hormones and can be influenced directly by them. In addition, cells in other brain areas have receptors for these hormones and thus may provide an indirect pathway to the hypothalamus. One such region is the area postrema, which is just dorsal to the solitary nucleus and projects to it. The area postrema is not protected by the blood-brain barrier (it is one of the circumventricular organs), and its neurons respond to cholecystokinin and GLP-1, which leads to decreased food intake.
Control of body weight over the long run is influenced by many factors and involves the interaction of the nervous and endocrine systems. In this section, the focus is on the role of hypothalamus and its control of the autonomic nervous system, which provides another example of how the hypothalamus is part of a servomechanism. In this case, adiposity is the controlled parameter. For further details on the endocrine system’s role, see
Early studies in which researchers used lesions and electrical stimulation provided evidence that the ventromedial and ventrolateral hypothalamus are involved in energy homeostasis. A lesion in the ventromedial region causes an increase in food intake (hyperphagia) that results in obesity, whereas electrical stimulation of the same region decreases feeding behavior. These lesions were also shown to alter autonomic activity, increasing parasympathetic and decreasing sympathetic tone, both of which lead to high blood insulin levels, which in turn promote energy conservation and storage (see ). These observations led to the idea that the ventromedial hypothalamus contains a satiety center. However, an alternative interpretation is that the primary controlled variable may not be simply eating behavior per se but rather body weight and, even more specifically, body fat levels (i.e., adiposity). Thus modulation of feeding behavior may be just one of several actions used to defend a body weight set point. Evidence for this is that although lesions cause an initial period of dynamic weight gain in which hyperphagia is present, this is followed by a static period in which the higher weight is maintained without hyperphagia. Moreover, animals with a lesion in the ventromedial hypothalamus that are fed a fixed (normal) amount of food to prevent hyperphagia nonetheless become obese, which implies changes in the regulation of other metabolic processes. Last, lesions of the ventromedial hypothalamus have been shown to alter levels of energy expenditure.